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The aim of this study was to investigate the association between socioeconomic status and erectile dysfunction. Data were obtained from the National Health and Nutrition Examination Survey, a nationally representative survey of the United States population. Socioeconomic status was estimated using the poverty income ratio, a ratio of family income to established poverty levels. Erectile function was assessed from a single survey question and was divided into two groups: normal (always and usually able to maintain an erection) and erectile dysfunction (sometimes or never able to maintain an erection). Multivariable logistic regression, using a multi-model approach, was used to characterize the interplay between well-established risk factors for erectile dysfunction and socioeconomic status. Our final cohort included 3679 respondents, representative of 81,255,155 subjects with a mean age of 44.4 [SE, 0.365]. Multivariable logistic regression showed that low-income respondents were significantly more likely to report erectile dysfunction [adjusted odds ratio (AOR) = 1.95, 95% CI 1.28-2.96; p = 0.003] compared to higher-income respondents. This study suggests that low socioeconomic status may be associated with erectile dysfunction in a large, nationally representative sample.

Gender dysphoria can present as a positive symptom of schizophrenia. Completion of gender affirmation surgeries should not occur as a result of male genital self‐mutilation via a deferral of emergent surgical reconstruction. Instead, gender affirmation should be considered after a full workup and assessment for resolution of any acute psychosis.

Summary Ganciclovir (GCV) inhibits spermatogenesis in preclinical studies but long‐term effects on fertility in renal transplant patients are unknown. In a prospective, multicenter, open‐label, nonrandomized study, male patients were assigned to Cohort A [valganciclovir (VGCV), a prodrug of GCV] (n = 38) or B (no VGCV) (n = 21) by cytomegalovirus prophylaxis requirement. Changes in semen parameters and DNA fragmentation were assessed via a mixed‐effects linear regression model accounting for baseline differences. Sperm concentration increased post‐transplant, but between baseline and treatment end (mean 164 days Cohort A, 211 days Cohort B), the model‐based change was lower in Cohort A (difference: 43.82 × 106/ml; P = 0.0038). Post‐treatment, sperm concentration increased in Cohort A so that by end of follow‐up (6 months post‐treatment) changes were comparable between cohorts (difference: 2.09 × 106/ml; P = 0.92). Most patients’ sperm concentration improved by end of follow‐up; none with normal baseline concentrations (≥20 × 106/ml) were abnormal at end of follow‐up. Changes in seminal volume, sperm motility/morphology, DNA fragmentation, and hormone levels were comparable between cohorts at end of follow‐up. Improvement in semen parameters after renal transplant was delayed in men receiving VCGV, but 6 months post‐treatment parameters were comparable between cohorts.

To determine if race/ethnicity impacts disclosure of erectile function.Data on age, education, erectile function, and past medical history were obtained from the National Health and Nutrition Examination Survey. Response rates to a single survey question regarding erectile function were calculated and compared between race/ethnicity groups. Two subgroups were created by excluding non-responders to questions about hypertension and prostate disease to control for overall non-responsiveness and urologic health literacy.Our final cohort consisted of 4,694 men. Overall, 3,898 (83.0%) responded to the erectile function survey question. Race/ethnicity was a significant factor in overall response rates to the Erectile function question: 85.2% in non-hispanic white, 82.3% in non-hispanic black, 81.2% in hispanic, and 64.8% in other subjects (P.001). Race/ethnicity remained significantly associated with responses rates among both subgroups. Multivariate logistic regression using the prostate disease subgroup showed that non-hispanic black (AOR = 2.02, 95% CI 1.01-4.03, P = .047) and hispanic (AOR = 2.18, 95% CI 1.19-4.00, P = .012) participants were significantly more likely to not disclose their erectile function compared to non-hispanic white participants after controlling for age and education.Non-hispanic black and hispanic men were significantly less likely to disclose their erectile function than non-hispanic white men in an anonymous, nationally representative survey. A better understanding of how cultural differences affect reporting of erectile function is important in improving patient care and accurately studying outcomes of urological procedures.

Men who ejaculate before or shortly after penetration, without a sense of control, and who experience distress related to this condition may be diagnosed with premature ejaculation (PE), while men who experience difficulty achieving sexual climax may be diagnosed with delayed ejaculation (DE). The experience of many clinicians suggest that these problems are not rare and can be a source of considerable embarrassment and dissatisfaction for patients. The role of the clinician in managing PE and DE is to conduct appropriate investigation, to provide education, and to offer available treatments that are rational and based on sound scientific data.The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. A research librarian conducted searches in Ovid MEDLINE (1946 to March 1, 2019), the Cochrane Central Register of Controlled Trials (through January 2019) and the Cochrane Database of Systematic Reviews (through March 1, 2019). An update search was conducted on September 5, 2019. Database searches resulted in 1,851 potentially relevant articles. After dual review of abstracts and titles, 223 systematic reviews and individual studies were selected for full-text dual review, and 8 systematic reviews and 59 individual studies were determined to meet inclusion criteria and were included in the review.Several psychological health, behavioral, and pharmacotherapy options exist for both PE and DE; however, none of these pharmacotherapy options have achieved approval from the United States Food and Drug Administration and their use in the treatment of PE and DE is considered off-label.Disturbances of the timing of ejaculation can pose a substantial impediment to sexual enjoyment for men and their partners. The Panel recommends shared decision-making as fundamental in the management of disorders of ejaculation; involvement of sexual partner(s) in decision making, when possible, may allow for optimization of outcomes.

INTRODUCTION AND OBJECTIVE:ChromaSelect is a highly sensitive and specific method of identification and isolation of intact and live human sperm from ejaculate, epididymal or testis specimens with ...

Background Ejaculation consists of the emission of semen from seminal vesicles and prostate, followed by expulsion. Ejaculatory dysfunction may take several forms including premature ejaculation, delayed or anejaculation, retrograde ejaculation, and painful ejaculation. Ejaculation is what we can see whereas orgasm is what we feel. The presence of ejaculate does not indicate the ability to experience orgasm. Hence, for the purpose of this work we consider orgasm and ejaculation as 2 separate neurobiological phenomena. Aim To review the role of advanced investigative techniques such as perineal ultrasound in the diagnosis and management of ejaculation and ejaculatory dysfunction. Methods We performed a PubMed search for key words individually and in combination: “ejaculation,” “ejaculatory dysfunction,” “delayed ejaculation,” “painful ejaculation,” “retrograde ejaculation,” “perineal ultrasound,” and “transrectal ultrasound.” We also share our local experience using perineal ultrasound in assessing ejaculation. Outcomes Perineal ultrasound can be used as an aid in the investigation of ejaculatory dysfunction. Results Evaluation of ejaculatory function hinges on a detailed psychosexual history and appropriate physical examination. Function of the ejaculatory center in the spine is androgen dependent; thus, hormonal evaluation is an important aspect of the workup. Disorders of ejaculation and orgasm require evaluation of neuromuscular reflexes activated during sexual activity. Dynamic ultrasonographic (US) ejaculatory-orgasmic studies allow for reproducible and detailed descriptions of the sexual response. Transrectal ejaculatory studies are useful in uncovering reasons for lack of antegrade semen emission, especially in men with poor sperm production or after vasectomy. Dynamic US studies contribute clinical utility in its non-invasive nature and can provide insight to the dynamic processes surrounding pelvic floor functioning in men. Conclusions Perineal US for men with delayed ejaculation or anejaculation, painful ejaculation, or retrograde ejaculation may be helpful in select cases. Further research using this modality may help advance our understanding of ejaculatory dysfunction. Forbes CM, Flannigan R, Paduch DA. Perineal Ultrasound: a Review in the Context of Ejaculatory Dysfunction. Sex Med Rev 2018;6:419–428.

Objective To evaluate whether varicocelectomy improves both serum testosterone and sexual function, as assessed by the Male Sexual Health Questionnaire (MSHQ). Methods A retrospective chart review of patients who have undergone varicocelectomy and had both pre- and postoperative MSHQ was performed. The MSHQ is a clinically validated questionnaire that assesses erectile function, ejaculatory function, and sexual satisfaction, with higher scores indicating better function. Clinical parameters pre and postvaricocelectomy were compared with paired t test. Results Thirty-four patients met study criteria. Seventeen patients (50%) presented for infertility, and the remaining 13 had symptomatic varicocele associated with hypogonadism. Average postsurgical follow-up was 20.6 ± 12.5 months. The majority of men in the study had bilateral varicoceles and left grade III varicoceles. Significant improvements in the total MSHQ score (3.9 ± 8.7, P = .027), the MSHQ erectile function (1.2 ± 2.3, P = .007), and the MSHQ ejaculatory function (1.4 ± 3.1, P = .018) domains were seen. Fifteen (44%) men saw improvement in their erectile function and 18 (53%) saw improvement in ejaculatory function. The improvement in serum testosterone was also significant (136.0 ± 201.3 ng/dL, P = .007). Conclusion Microsurgical repair of varicocele not only improves testosterone, but also improves patient-reported erectile and ejaculatory functions. Patients can confidently be counseled that varicocelectomy has the potential to improve sexual function along with serum testosterone.

Study question Do human Sertoli cells in testes that exhibit the Sertoli cell-only (SCO) phenotype produce substantially less glial cell line-derived neurotrophic factor (GDNF) than Sertoli cells in normal testes? Summary answer In human SCO testes, both the amounts of GDNF mRNA per testis and the concentration of GDNF protein per Sertoli cell are markedly reduced as compared to normal testes. What is known already In vivo, GDNF is required to sustain the numbers and function of mouse spermatogonial stem cells (SSCs) and their immediate progeny, transit-amplifying progenitor spermatogonia. GDNF is expressed in the human testis, and the ligand-binding domain of the GDNF receptor, GFRA1, has been detected on human SSCs. The numbers and/or function of these stem cells are markedly reduced in some infertile men, resulting in the SCO histological phenotype. Study design, size, and duration We determined the numbers of human spermatogonia per mm2 of seminiferous tubule surface that express GFRA1 and/or UCHL1, another marker of human SSCs. We measured GFRA1 mRNA expression in order to document the reduced numbers and/or function of SSCs in SCO testes. We quantified GDNF mRNA in testes of humans and mice, a species with GDNF-dependent SSCs. We also compared GDNF mRNA expression in human testes with normal spermatogenesis to that in testes exhibiting the SCO phenotype. As controls, we also measured transcripts encoding two other Sertoli cell products, kit ligand (KITL) and clusterin (CLU). Finally, we compared the amounts of GDNF per Sertoli cell in normal and SCO testes. Participants/materials setting methods Normal human testes were obtained from beating heart organ donors. Biopsies of testes from men who were infertile due to maturation arrest or the SCO phenotype were obtained as part of standard care during micro-testicular surgical sperm extraction. Cells expressing GFRA1, UCHL1 or both on whole mounts of normal human seminiferous tubules were identified by immunohistochemistry and confocal microscopy and their numbers were determined by image analysis. Human GDNF mRNA and GFRA1 mRNA were quantified by use of digital PCR and Taqman primers. Transcripts encoding mouse GDNF and human KITL, CLU and 18 S rRNA, used for normalization of data, were quantified by use of real-time PCR and Taqman primers. Finally, we used two independent methods, flow cytometric analysis of single cells and ELISA assays of homogenates of whole testis biopsies, to compare amounts of GDNF per Sertoli cell in normal and SCO testes. Main results and the role of chance Normal human testes contain a large population of SSCs that express GFRA1, the ligand-binding domain of the GDNF receptor. In human SCO testes, GFRA1 mRNA was detected but at markedly reduced levels. Expression of GDNF mRNA and the amount of GDNF protein per Sertoli cell were also significantly reduced in SCO testes. These results were observed in multiple, independent samples, and the reduced amount of GDNF in Sertoli cells of SCO testes was demonstrated using two different analytical approaches. Large scale data N/A. Limitations, reasons for caution There currently are no approved protocols for the in vivo manipulation of human testis GDNF concentrations. Thus, while our data suggest that insufficient GDNF may be the proximal cause of some cases of human male infertility, our results are correlative in nature. Wider implications of the findings We propose that insufficient GDNF expression may contribute to the infertility of some men with an SCO testicular phenotype. If their testes contain some SSCs, an approach that increases their testicular GDNF concentrations might expand stem cell numbers and possibly sperm production. Study funding/competing interest(s) This research was funded by the Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Centers for Translational Research in Reproduction and Infertility Program (NCTRI) Grant 1R01HD074542-04, as well as grants R01 HD076412-02 and P01 HD075795-02 and the U.S.-Israel Binational Science Foundation. Support for this research was also provided by NIH P50 HD076210, the Robert Dow Foundation, the Frederick & Theresa Dow Wallace Fund of the New York Community Trust and the Brady Urological Foundation. There are no competing interests.

To assess the efficacy of time-resolved MR angiography (MRA) in evaluating penile vasculature in patients with clinically suspected vascular anomalies contributing to their erectile dysfunction correlating with penile doppler ultrasound (PDUS) findings and clinical outcomes after surgical intervention. Men (n = 26) with signs of early vascular shunting on PDUS underwent time-resolved, contrast-enhanced (0.1 mMol/kg gadobutrol at 1 ml/s followed by saline flush) 3-dimensional spoiled gradient echo T1-weighted MRA sequence performed over 3 min with 4.6 s frame rate after intracavernosal injection of an erectogenic agent. Additional T1- and T2-weighted sequences were performed for anatomic co-localization and tissue characterization. MRA images were evaluated for early filling of draining veins as well as arteriovenous malformations and fistulas and correlated with findings at surgery. 29 MRA examinations on 26 patients (mean age 39 years) demonstrated abnormal early venous drainage (n = 22) as well as diminutive/delayed cavernosal enhancement (n = 3), incomplete tumescence (n = 2), and combined arterial inflow/venous outflow disease (n = 1). The MRA had a concordance of 85.2% at determining the presence, or lack thereof of a shunt/AVM when compared to PDUS. Time-resolved MRA allows for both temporal and spatial resolution with visualization of both arterial and venous abnormalities which may be suggested with a screening PDUS examination. This technique allows us to provide detailed anatomic information prior to any surgical intervention.

Sertoli cell-only (SCO) syndrome is a severe form of human male infertility seemingly characterized by the lack all spermatogenic cells. However, tubules of some SCO testes contain small patches of active spermatogenesis and thus spermatogonial stem cells. We hypothesized that these stem cells cannot replicate and seed spermatogenesis in barren areas of tubule because as-of-yet unrecognized deficits in Sertoli cell gene expression disable most stem cell niches. Performing the first thorough comparison of the transcriptomes of human testes exhibiting complete spermatogenesis with the transcriptomes of testes with SCO syndrome, we defined transcripts that are both predominantly expressed by Sertoli cells and expressed at aberrant levels in SCO testes. Some of these transcripts encode proteins required for the proper assembly of adherent and gap junctions at sites of contact with other cells, including spermatogonial stem cells (SSCs). Other transcripts encode GDNF, FGF8 and BMP4, known regulators of mouse SSCs. Thus, most SCO Sertoli cells can neither organize junctions at normal sites of cell-cell contact nor stimulate SSCs with adequate levels of growth factors. We propose that the critical deficits in Sertoli cell gene expression we have identified contribute to the inability of spermatogonial stem cells within small patches of spermatogenesis in some SCO testes to seed spermatogenesis to adjacent areas of tubule that are barren of spermatogenesis. Furthermore, we predict that one or more of these deficits in gene expression are primary causes of human SCO syndrome.

INTRODUCTION AND OBJECTIVES:Chromatin-modifying complexes (CPCs) play a critical role in epigenetic gene regulation and are thought to implement global genetic programs. Several long non-coding RNA...

INTRODUCTION AND OBJECTIVES:Our group has previously demonstrated that men with Sertoli Cell Only Syndrome (SCO) demonstrate a 17x downregulation of miR-202-5p compared to testis biopsies from norm...

The ability of men to remain fertile throughout their lives depends upon establishment of a spermatogonial stem cell (SSC) pool from gonocyte progenitors, and also maintaining the proper balance between SSC renewal and spermatogenic differentiation throughout life. Depletion of SSCs causes infertility with a Sertoli Cell Only Syndrome (SCOS) phenotype. We previously created a mouse strain in which an inhibitory phosphorylation site (Tyr15) of Cyclin-dependent kinase 2 (Cdk2) was altered. Juvenile males homozygous for this allele (Cdk2Y15S) initiate the first round of spermatogenesis, which originates from prospermatogonia, but meiocytes arrest due to chromosomal defects resembling those inCdk2-/-mice. Subsequent waves of spermatogonial differentiation and meiosis were largely absent, leading to an SCOS-like phenotype. Here, we demonstrate thatCdk2Y15S/Y15Smice possess mitotically active GFRa1+SSC-like cells, but they are impaired in their ability to differentiate. Marker analysis and single cell RNA-seq revealed defective differentiation of gonocytes into SSCs. Biochemical and genetic data demonstrated thatCdk2Y15Sis a gain-of-function allele causing deregulated kinase activity, and its phenotypic effects could be reversed by mutating the Thr160 positive regulatory site incis. These results demonstrate that precise temporal regulation of CDK2 activity in male germ cell development and in the cell cycle is critical for long-term spermatogenic homeostasis.

Background Mechanisms underlying delayed orgasm (DO) are poorly understood; however, known effects of psychotropic medications on sexual function provides a rationale for aberrant central nervous system signaling as a cause. Aim To compare brain activation between men with normal orgasm and those with lifelong DO during sexual stimulation using brain fMRI algorithms. Methods 3 subjects with self-reported life-long DO and 6 normal controls were included in this study. The International Index of Erectile Function, Male Sexual Health Questionnaire, and self-reported time to orgasm were used to assess sexual function. Subjects underwent a 3-T fMRI study while viewing 3 video clips: a neutral control (NC), a positive emotional control (EC), and a sexual condition (SC). Each video sequence was repeated 5 times, with 50-second clips presented in a randomized fashion. fMRI data were analyzed in a block design manner to determine areas of differential brain activation between groups. The Allen Brain Atlas of gene expression in the human brain was used to identify signaling pathways in the areas of differential fMRI activation between the DO and control groups. Outcomes The primary outcome was differential activation of fMRI neural activation between groups. Results Analysis of differential activation in the SC compared with the NC and EC revealed increased activation in the right frontal operculum (P = .003), right prefrontal gyrus (P = .003), and inferior occipital gyrus (P = .003). Increased activation in the right fusiform gyrus of the occipital lobe and the right hippocampus (P = .0004) was seen in the DO group compared with controls. Using the Allen Atlas of Human Brain Expression, we identified corresponding neurotransmitter receptors to this region, including adenosine receptors, muscarinic and nicotinic cholinergic receptors, cannabinoid receptors, and dopamine receptors, among others. Clinical Implications Lifelong DO in men may be due to abnormal neurotransmitter signaling leading to poor progression of arousal due to aberrant processing of sexual cues. Identification of neurotransmitter pathways by fMRI will aid the development of pharmacotherapeutic agents. Strengths & Limitations Strengths of this study include the novel application of functional neuroimaging to investigate the pathogenesis of DO. Limitations include the small sample size, making this study exploratory in nature. Conclusion This study revealed differences in brain activation on visualization of sexual stimuli in men with a history of DO compared with controls. Identified regions are rich in numerous neurotransmitter receptor subtypes and may be amenable to pharmacologic targeting to identify novel therapies for these men.

IntroductionYBX2 protein binds to Y-box promotors and to mRNAs in the cytoplasm of pachytene spermatocytes and round spermatids in rodents. Knock-out of YBX2 leads to maturation arrest in animal models. YBX2 binds PRM1 and 2 mRNA, which is transcribed early and sequestrated for translation during late spermatogenesis.ObjectiveThis study aimed to determine if the loss of YBX2 is associated with MA arrest due to the loss of sequestration of protamines in the human testis. As a second aim, we examined the expression of YBX2, and its transcription factors in maturation arrest (MA)(early and late) and normal controls in men.MethodsRNAseq was performed using RNA extracted from human testis samples from 44 men with non-obstructive azoospermia and ten from healthy controls. Differential expression was performed using JMPgenomics, FDRResultsExpression ofYBX2mRNA was significantly downregulated in early and late MA compared to controls. Surprisingly, PRM1&2 mRNAs were also depleted in men with MA. Multifactorial regression analysis demonstrated a decrease in YBX2 expression in MA is due to decrease in COMP levels (pConclusionsDecrease in YBX2 protein expression in men with LMA leads to loss of translational suppression and lack of PRM1 and PRM2 necessary to complete spermatogenesis.

Introduction Penile transplantation, in its infancy, has the potential to reestablish functional outcomes for men with penile loss and disfigurement. However, significant bioethical considerations are pertinent, and systematic discussions are necessary to safely progress implementation. Aim To determine the attitude of health practitioners toward the penile transplant and identify the key aspects of concern pertinent to the operation and clinical care. Methods Health care professionals from the United States responded to either email invitation, web link, or social media post on Facebook to complete a questionnaire investigating perceptions and attitudes toward penile transplantation. Main Outcome Measures Respondents' attitude toward penile transplantation, their own perceived important functions of the penis, and concerns about performing a penile transplantation. Respondents' previous exposure to visceral transplants, to penile disfigurement, and information about penile transplants were used as independent factors in analysis. Results Among 412 health care professionals who responded to the questionnaire, 95.9% were in favor of visceral organ transplant, but only 64.3% were in favor of penile transplantation. The results showed that 61.3% of respondents first learned about the penile transplant from mass media, whereas only 37.5% had been exposed through a scientific journal, formal lecture, or a professional colleague. Younger health professionals and those exposed through professional forums surrounding penile transplantation were more likely to be in favor of the procedure (P < .001). The most important functions of the penis were identified by respondents as being sexual function (role in sexual activity) and gender identity (being a man) with rates of 86.4% and 85.3%, respectively (P < .001). Barriers identified by respondents included the use of immunosuppression and the potential subsequent effect on healthcare resource utilization. Reading an excerpt about penile trauma in war during the questionnaire improved acceptance of penile transplantation (P = .05). Conclusion Penile transplantation is accepted by most health professionals surveyed. Younger respondents and those informed through professional outlets are more favorable toward penile transplantation. Anticipated limitations include the risk of immunosuppression, lack of available donors, and the effect on healthcare utilization.

Introduction Ejaculatory dysfunctions other than premature ejaculation are commonly encountered in specialized clinics; however, their characterization in community-dwelling men is lacking. Aim The aim of this study was to evaluate the prevalence, severity, and associated distress of four ejaculatory dysfunctions: delayed ejaculation (DE), anejaculation (AE), perceived ejaculate volume reduction (PEVR) and/or decreased force of ejaculation (DFE) as a function of demographic and clinical characteristics in men. Methods Observational analysis of 988 subjects presenting with one or more types of ejaculatory dysfunctions other than premature ejaculation who screened for a randomized clinical trial assessing the efficacy of testosterone replacement on ejaculatory dysfunction. Demographic and clinical characteristics were assessed as potential risk factors using regression analysis. Main Outcome Measures The main outcome measures used were ejaculatory dysfunction prevalence and scores (3-item Men’s Sexual Health Questionnaire Ejaculatory Dysfunction-Short Form [MSHQ-EjD-SF]), and bother (MSHQ-EjD-SF Bother item) and sexual satisfaction/enjoyment (International Index of Erectile Function Questionnaire Q7, Q8) as a function of subject’s age, race, body mass index (BMI) and serum testosterone levels (measured by liquid chromatography tandem mass spectrometry). Results Mean (standard deviation [SD]) age of the participants was 52 years (11). Eighty-eight percent of the men experienced more than one type of ejaculatory dysfunction and 68% considered their symptoms to be bothersome. Prevalence of the ejaculatory dysfunctions was substantial across a range of age, race, BMI, and serum testosterone categories. Prevalence of PEVR and DFE were positively associated with age ( Conclusion The majority of the participants experienced multiple ejaculatory dysfunctions and found them to be highly bothersome. Ejaculatory dysfunctions were prevalent across a wide range of demographic and clinical characteristics.

Objective To evaluate assisted reproductive technology (ART) outcomes using testicular sperm in oligospermic men who previously failed to achieve paternity using TUNEL-positive ejaculated sperm. Design Retrospective cohort. Setting Academic medical center. Patient(s) Twenty-four oligospermic men who failed one or more ART cycles using ejaculated sperm with TUNEL-positive proportion >7%, and subsequently underwent microsurgical testicular sperm extraction (TESE). Intervention(s) TESE followed by intracytoplasmic sperm injection (ICSI). Main Outcome Measure(s) TUNEL-positive level in ejaculated and testicular sperm; clinical pregnancy. Result(s) The mean TUNEL-positive level was 24.5% for ejaculated sperm, and 4.6% for testicular sperm. Clinical pregnancy was achieved in the first ART cycle with testicular sperm in 12 (50%) out of 24 couples. There was no statistically significant difference in maternal and paternal age, maternal gravity and parity, number of previous ART attempts, concentration or motility of retrieved sperm, number of oocytes retrieved, fertilization rate, or number of embryos transferred between couples who did and did not achieve pregnancy. No miscarriages occurred. All 12 pregnancies resulted in the delivery of healthy children. Conclusion(s) The percentage of TUNEL-positive cells is lower in testicular sperm for oligospermic men who have abnormal ejaculated sperm DNA fragmentation. The use of testicular sperm for ICSI was associated with a 50% pregnancy and live-birth rate for couples who had previously failed one or more IVF–ICSI cycles with ejaculated sperm. No other clinical predictors of successful pregnancies after the use of surgically retrieved sperm could be identified. In men with elevated TUNEL-positive ejaculated sperm and failed ART, TESE may be considered.

Objective To evaluate the relationship of testosterone-enhancing therapy on alkaline phosphatase (AP) in relation to bone mineral density (BMD) in hypogonadal men. Patients and Methods Retrospective review of 140 men with testosterone levels of

Introduction Klinefelter syndrome (KS) is the result of sex chromosome aneuploidy most often characterized as 47,XXY. The typical features of KS include tall stature, gynecomastia, small firm testicles, hypergonadotropic hypogonadism, and infertility. However, abnormalities in neurodevelopment, cognition, and social and behavioral functioning also can be present. The abnormalities in neurodevelopment are believed to be due in part to androgen deficiency during early development and puberty. Aim To discuss the role of androgens in normal adolescent development; discuss the cognitive, behavioral, and social functioning of children with KS; evaluate the evidence for early androgen therapy in men with KS; and discuss management strategies in the development of boys with KS. Methods A systematic review of early androgen therapy and KS was performed using PubMed-Medline and Scopus databases. Relevant articles commenting on social, behavioral, cognitive, and physical outcomes among infants, children, and adolescents were included for reporting and discussion. Main Outcome Measures Social and behavior functioning; cognitive outcomes; adverse effects associated with androgen therapy. Results 3 retrospective articles and 2 randomized controlled trials addressing early androgen therapy in boys with KS were reviewed. These studies showed an improvement in several aspects of social and cognitive functioning based on validated questionnaires. Treatment strategies, potential negative effects, and limitations of the literature on early androgen therapy in boys with KS are discussed. Conclusion Our findings indicate that early androgen supplementation in children with KS combined with specific educational, family, and social support improves behavioral functioning. The optimal timing of hormonal therapy might require prospective studies, but based on our data and review of the literature, the benefit of early hormonal and therapeutic intervention in KS is very encouraging. Flannigan R, Patel P, Paduch DA. Klinefelter Syndrome. The Effects of Early Androgen Therapy on Competence and Behavioral Phenotype. Sex Med Rev 2018;6:595–606.

The aim of this study was to design a molecular assay for the diagnosis of Klinefelter syndrome (KS), based on the detection of supernumerary X-chromosomes (X-chs). DNA was extracted from peripheral blood samples of twenty-six 47,XXY males; two 46,XY/47,XXY males; twenty-two 46,XY males; and 15 females; and deaminated. Methylation-specific quantitative polymerase chain reaction (MS-qPCR) was performed using primers for unmethylated and methylated copies of the X-ch inactive-specific transcript (XIST-U and XIST-M) gene. X-ch disomy was determined on the basis of XIST methylation status. Degree of mosaicism in the 46,XY/47,XXY males was compared with karyotype and fluorescent in situ hybridization (FISH) results. Data analysis was performed using the Roche® LightCycler software V. 3.5.3., including determination of crossing points (CPs) by fit-point analysis and melting curve analysis. X-ch disomy was detected in all female controls and KS patients; male controls expressed XIST-M only. CPs ranged from 29.5 to 32.5 (standard deviation (s.d.) 0.8) for XIST-U and from 29 to 31 (s.d. 0.6) for XIST-M. Limit of detection of mosaicism was 1%. Based on XIST-U/XIST-M ratios for the two 47,XXY/46,XY patients, the calculated degree of mosaicism (1.8% and 17.8%) was comparable to FISH results (2.3% and 15%, respectively). Turnaround time from DNA deamination to final data analysis was under 9 h. We conclude that MS-qPCR is a sensitive, specific and rapid test for the detection of X-ch disomy, with applicability for the screening and diagnosis of KS, even in the setting of low grade 47,XXY/46,XY mosaicism.

We investigated the safety and tolerability of testosterone replacement therapy in adolescents with Klinefelter syndrome.We reviewed the medical records of all consecutive adolescents with Klinefelter syndrome evaluated between 2007 and 2012. Patients receiving testosterone replacement and aromatase inhibitor therapy were identified. Data on demographics, physical characteristics, medical history and serum hormone concentrations were collected for each patient. We evaluated longitudinal changes in serum testosterone, luteinizing hormone and follicle-stimulating hormone as well as changes in body mass index after the initiation of testosterone replacement therapy.We identified 151 adolescents with Klinefelter syndrome. Mean age at presentation was 11.6 years. Testosterone replacement therapy and aromatase inhibitors were initiated in 110 and 75 patients, respectively, at an average age of 13 to 14 years. Topical testosterone replacement therapy was used in 95% of patients with good clinical efficacy and compliance based on serial serum testosterone values. After the initiation of testosterone replacement therapy average serum testosterone improved from 240 to 650 ng/ml. Serum luteinizing hormone and follicle-stimulating hormone increased with the progression of puberty from 2.6 to 16.6 and 7 to 42 mIU/ml, respectively. No adverse outcomes related to testosterone replacement therapy were reported.Hormone supplementation with testosterone and aromatase inhibitors in adolescents with Klinefelter syndrome appears to be safe and effective for maintaining serum testosterone within the normal range. Compliance with topical formulations is high. Topical testosterone replacement therapy is not associated with the suppression of endogenous serum luteinizing hormone or follicle-stimulating hormone.

Sperm chromatin damage has been associated with male infertility, increased risk for spontaneous abortion, and poor embryo development. Available methods for detecting chromatin damage render the sperm no longer suitable for clinical use. Early apoptotic events resulting in chromatin damage are associated with increased permeability of the cell membrane to large ions. We propose the use of a large fluorescent organic cation, proprietary fluorochrome (PF-1), for fluorescence-activated cell sorting (FACS) for negative selection of sperm without chromatin damage. Sperm with chromatin damage are PF-1 positive. Performance of cell sorting by PF-1 was verified with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) after FACS on PF-1(+) and PF-1(-) subpopulations. Whereas 19.5% of PF-1 positive sperm were TUNEL positive only 1.5% sperm in the PF-1(-) fraction were TUNEL positive (p 0.00001). TUNEL values below 1.9% were considered background fluorescence. Post-sorting motility and vitality were 49.4% (SD: 12.5) and 65.0% (SD: 14.99), respectively. Proprietary fluorochrome activated sperm sorting may decrease or most likely eliminate all of TUNEL positive sperm without adverse effects on viability, providing a new therapeutic avenue for men with a high percentage of TUNEL positive sperm. Further research is needed to determine if the reduction in TUNEL positive sperm using PF-1 will improve in vitro fertilization (IVF) outcomes.

What's known on the subject? and What does the study add? Disorders of ejaculation and orgasm are common, even in men with only mild erectile dysfunction (ED). Treatment with the phosphodiesterase type-5 inhibitor tadalafil was associated with improvements in ejaculatory and orgasmic function. Patients with residual ejaculatory or orgasmic dysfunction experience reduced sexual satisfaction. These findings need to be corroborated in further clinical trials involving men without ED. Objectives To compare effects of tadalafil on ejaculatory and orgasmic function in patients presenting with erectile dysfunction (ED). To determine the effects of post-treatment ejaculatory dysfunction (EjD) and orgasmic dysfunction (OD) on measures of sexual satisfaction. Patients and Methods Data from 17 placebo-controlled 12-week trials of tadalafil (5, 10, 20 mg) as needed in patients with ED were integrated. EjD and OD severities were defined by patient responses to the International Index of Erectile Function, question 9 (IIEF-Q9; ejaculation) and IIEF-Q10 (orgasm), respectively. Satisfaction was evaluated using the intercourse and overall satisfaction domains of the IIEF and Sexual Encounter Profile question 5. Analyses of covariance were performed to compare mean ejaculatory function and orgasmic function, and chi-squared tests evaluated differences in endpoint responses to IIEF-Q9 and IIEF-Q10. Results A total of 3581 randomized subjects were studied. Treatment with tadalafil 10 or 20 mg was associated with significant increases in ejaculatory and orgasmic function (vs placebo) across all baseline ED, EjD, and OD severity strata. In the tadalafil group, 66% of subjects with severe EjD reported improved ejaculatory function compared with 36% in the placebo group (P < 0.001). Similarly, 66% of the tadalafil-treated subjects (vs 35% for placebo; P < 0.001) with severe OD reported improvement. Residual severe EjD and OD after treatment had negative impacts on sexual satisfaction. Limitations of the analysis include its retrospective nature and the use of an instrument (IIEF) with as yet unknown performance in measuring treatment responses for EjD and OD. Conclusions Tadalafil treatment was associated with significant improvements in ejaculatory function, orgasmic function and sexual satisfaction. Proportions of subjects reporting improved ejaculatory or orgasmic function were ≈ twofold higher with tadalafil than with placebo. These findings warrant corroboration in prospective trials of patients with EjD or OD (without ED).

47, XXY or Klinefelter syndrome (KS), the most common chromosomal aberration in males, is characterized by either absolute or relative hypogonadism with frequent decline in serum testosterone (T) following the onset of puberty. Decreased T levels are the result of testicular dysfunction with decrease in size of Leydig cells, and loss of germs and Sertoli cells leading to tubular hyalinization. Increase in estradiol results from over-expression of aromatase CYP19. Deficient androgen production and observed varied response of end-organs to T leads to delayed progression of puberty with decreased facial/body hair, poor muscle development, osteoporosis, and gynecomastia. It is possible that hypogonadism and excessive estradiol production contribute to emotional and social immaturity, and specific learning disabilities in KS. Based on the authors' experience and literature review, early fertility preservation and hormonal supplementation may normalize pubertal development, prevent metabolic sequelae of hypogonadism, and have a positive effect on academic and social development. No randomized clinical trials are available studying the effects of T supplementation on reproductive or cognitive issues in KS. Aggressive T supplementation (topical gel) and selective use of aromatase inhibitors may be considered at the onset of puberty with careful follow-up and titration to reach age-specific high-normal physiologic serum values. The decision to institute hormonal therapy should be part of a multidisciplinary approach including physical, speech, behavioral, and occupational therapy. © 2013 Wiley Periodicals, Inc.